Apremilast is a selective inhibitor of phosphodiesterase 4 (PDE4) specific for cyclic adenosine monophosphate (cAMP). The inhibition of PDE4 results in increased intracellular cAMP levels. Apremilast is chemically named N-[2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]acetamide, and is represented by the following chemical structure:

Apremilast is approved in the United States for treatment of adults with active psoriatic arthritis. It is also being tested for treating other chronic inflammatory diseases such as psoriasis, ankylosing spondylitis, Behcet's disease, and rheumatoid arthritis. The specific mechanism(s) responsible to the apremilast's therapeutic action in psoriatic arthritis patients is not well defined.
U.S. Pat. No. 6,020,358 discloses substituted phenethylsulfones, including apremilast, and methods of use thereof for reducing TNFα levels.
WO 2003/080048 and WO 2003/080049 disclose the use of the (−) and (+) enantiomers of apremilast, respectively, in the treatment or prevention of diseases or disorders by the inhibiting TNF-α production or PDE4.
WO 2009/120167 discloses seven solid forms of the (+) enantiomer of apremilast, designated as Forms A to G, including methods of preparation. The crystalline form A is characterized by diffraction peaks in the X-ray powder diffraction pattern at 8.1°, 15.2°, 17.4°, 23.6° and 25.1° degrees 2θ. The crystalline form B is characterized by diffraction peaks in the X-ray powder diffraction pattern at 10.1°, 13.5°, 20.7° and 26.9° degrees 2θ. The crystalline form C is characterized by peaks in the X-ray powder diffraction pattern at 7.5°, 11.3°, 16.4°, 17.8° and 26.4° degrees 2θ. The crystalline form D is characterized by diffraction peaks in the X-ray powder diffraction pattern at 7.5°, 11.3°, 16.3°, 25.2° and 26.0° degrees 2θ. The crystalline form E is characterized by peaks in the X-ray powder diffraction pattern at 7.6°, 9.2°, 11.4°, 17.9° and 26.6° degrees 2θ. The crystalline form F is characterized by diffraction peaks in the X-ray powder diffraction pattern at 8.1°, 8.6°, 15.6°, 17.3° and 25.4° degrees 2θ. The crystalline form G is characterized by diffraction peaks in the X-ray powder diffraction pattern at 7.9°, 11.7°, 16.8°, 18.1° and 26.7° degrees 2θ. WO 2009/120167 also generally mentions an amorphous form of apremilast but does not teach that a single amorphous form was actually obtained or characterized.
A new crystalline or amorphous form of a compound may possess physical properties that differs from, and is advantageous over, those of other crystalline or amorphous forms. These include, packing properties such as molar volume, density and hygroscopicity; thermodynamic properties such as melting temperature, vapor pressure and solubility; kinetic properties such as dissolution rate and stability under various storage conditions; surface properties such as surface area, wettability, interfacial tension and shape; mechanical properties such as hardness, tensile strength, compatibility, handling, flow and blend; and filtration properties. Variations in any one of these properties may affect the chemical and pharmaceutical processing of a compound as well as its bioavailability and may often render the new form advantageous for pharmaceutical and medical use.
There remains an unmet need for additional solid state forms of apremilast having good physiochemical properties, desirable bioavailability, and advantageous pharmaceutical parameters.